A generalized stochastic Markov model describing interactive gating of ion channels.
Marsh, Daniel
Patch-clamp is a powerful technique to study ion channel currents.
In general, patch clamp recordings from membrane patches containing
multiple channels exhibit an independent gating behavior consistent with
binomial probability distribution. However in some preparations,
observations suggest a cooperative gating behavior among channels that
does not follow a binomial distribution. To understand this, consider a
system of two-channels. Let the probability of observing 2-closed,
1-open, and 2-open current levels be [A.sub.0], [A.sub.1], and
[A.sub.2]. For independently gating channels, the ratios [A.sub.0]:
[A.sub.1]: [A.sub.2] = 1: 2r: r2, where r is the ratio of open to closed
probability of a single channel. Previously, a model based on
steady-state probabilities has been formulated to describe cooperative
ion channel gating with two additional parameters, rc and ro,
representing closed-closed and open-open interactions. This gives
[A.sub.0]: [A.sub.1]: [A.sub.2] = (1 + rc): 2r: [r.sup.2](1 +
[r.sub.0]). This paper extends the previous model by enumerating all
possible combinations of states in an interacting N-channel system with
one additional parameter, rb, denoting closed-open interactions. For two
channels, this model yields [A.sub.0]: [A.sub.1]: [A.sub.2] = (1 + rc):
2r(1 + rb): [r.sup.2](1 + [r.sub.0].). This model provides exact
expressions for three- and four- channels system, and a procedure to
analyze an arbitrary number of channels. Ion channels are major drug
targets, and the scientific community and the pharmaceutical industry
are substantially invested in the endeavor to understand them. This
mathematical model will facilitate quantitative analysis and
interpretation of cooperative ion channel gating in living systems.
* Summers, M.W. and K. Manivannan. Department of Physics, Astronomy
and Materials Sciences, Southwest Missouri State University.